2, 2-diphenyl-1, 3-propanediol monocarbamate



Patented Get. 20, 195 3 UNITED STATES PATENT .o-rrics az-mrnnm-m-rnoraiwsnron MONOCARBAMATE Frank M. Berger, Princeton, and Bernard J. Ludwig, North Brunswick, N. J assignors to Carter Products, Inc., New York,

of Maryland N. Y., a corporation No Drawing. Application January 4, 1952, Serial No. 265,056

cam onion The compound may also be named 2,2 -diphenyl-3-hydroxypropyl carbamate. The compound is a white crystalline solid melting at from 121-122 C., it is only slightly soluble in water at ordinary room temperature, and has exceptional anticonvulsant properties.

The 2,2 disubstituted 1,3 propanediols are short acting anticonvulsant drugs and the dicarbamate derivatives have a longer duration of anticonvulsant action. The monocarbamates in general resemble the parent compounds, the diols, in that they have a short duration of activity. We have discovered, however, that 2,2-di henyl- 1,3-propanedio1 monocarbamate possesses an unexpectedly long duration of anticonvulsant activity. It was surprising also that th corresponding dicarbamate, 2,2-dipheny1-1,3-pr0panediol dicarbamate, has very low activity, even below that of the parent diol. The near homologs of the monocarbamate also have low activity. The anticonvulsant properties of 2,2-diphenyl-1,3-propanedio1 monocarbamate are abnormal in comparison with its most closely related compounds.

The compound of the invention can be prepared by the low temperature reaction of 1 mole of 2,2-dipheny1-1,3-propanediol with 1 mole of phosgene in an inert medium in the presence of a tertiary amine followed by the conversion of the chlorocarbonate derivative to the desired amide. One suitable method of preparing 2,2-diphenyl-1,3-propanediol is described by Dieter G. Markees and Alfred Burger, J. A. C. S., 71: 2034, 1949. However, because of the presenc of two reactive centers in both of the reactants (diol and phosgene) this procedure yields, in addition to the desired monocarbamate derivative, considerable amounts of unreacted diol as well as the dicarbamate. The diificulty of separating these products is avoided by forming the monocarbamate through ammonolysis of the cyclic carbonate ester. The latter compound was prepared by the reaction of equimolar quantities of phosgene and the diol under controlled conditions. The preferred method of preparing 2,2- diphenyl -3- hydroxypropyl carbamate involves the following equation:

CeHs CHzOH CaHs CHiOH The following is an example of one method of producing the compound of the invention:

Fifteen parts of 2,2-diphenyl-1,3-propanedio1 and 25 parts of antipyrine are dissolved while stirring in parts of chloroform. To this solution there is added with continuou stirring 7 parts of phosgene dissolved in 150 parts of chloroform, at a rate sufficient to maintain the temperature of the reaction at from 10 C, to 15. C. Stirring is continued and the mixture is allowed to warm to approximately 25 C. Any solid antipyrine hydrochloride that separates on standing is removed by filtration, and the filtrate is concentrated by removal of the major portion of the solvent. The concentrate is freed from watersoluble components by water extraction. Upon removal of the remaining solvent, there is obtained from 5 to 10 parts of the cyclic carbonate ester of 2,2-diphenyl-1,3-propanedi0l. Recrystallization from ethyl alcohol gives a product melting at from 156 to 158 C. Twenty-five parts of the carbonate and 9 parts of liquid ammonia are placed in a steel pressure vessel and allowed to warm to room temperature. After standing for from 24 to 72 hours, the contents of the vessel are removed, the excess ammonia allowed to evaporate, and the residue recrystallized from Water. From 20 to 25 parts of 2,2 diphenyl 1,3 propanediol monocarbamate (2,2-diphenyl-3-hydroxypropyl carbamate) are obtained. The compound has a, melting point 121-122 C. Analysis calculated for CmI-InNOa: c 71.28; H 6.39; N 5.21. Found by analysis: 0 References Cited in e fi of this p t V0.83; 1-16.27; N 5.17. FOREIGN PATENTS We claim:

. Number Country Date The compound 2,2 dlphenyl- 1,3.- propanea diol monocarbamate which is represented by the 614295 Great Bntam 1948 formula OTHER REFERENCES 0.11 011,011 Berger, Chemical Abstracts, vol. 43, p. 8546 Calif CHaOCfll-NHI FRANK M. BERGER. BERNARD JQLUDWIG. 

